Andamertinib With or Without Platinum-doublet Chemotherapy Versus Platinum-doublet Chemotherapy in Patients With NSCLC Harboring Atypical EGFR Mutations

Официальное название

An Open-label, Randomized, Multicenter Phase II/III Study to Evaluate the Efficacy and Safety of Andamertinib With or Without Platinum-doublet Chemotherapy Versus Platinum-doublet Chemotherapy in Patients With Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Harboring Atypical EGFR Mutations Who Have Not Received Prior Systematic Therapy

Обзор

This study is an open-label, randomized, multicenter phase II/III clinical trial designed to evaluate the efficacy, safety, and tolerability of Andamertinib with or without platinum-based chemothsrapy versus platinum-based chemotherapy in previously untreated participants with locally advanced or metastatic non-squamous NSCLC harboring EGFR atypical mutations. The study comprises two stages: phase II (dose-exploration stage) and phase III (pivotal study stage)

Подробное описание

This a three-stage study consist a Screening Phase (Day -28 to -1), a Treatment Phase (until treatment discontinuation), and a Follow-up Phase (including end of treatment visit (EOT),end of study visit(EOS), safety follow-up and survival follow-up).

Вмешательства

• Препарат PLB1004
  Andamertinib with or without platinum-based chemothsrapy versus platinum-based chemotherapy

Первичные конечные точки

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]). [Срок оценки: Up to 3 years]
• RP3D or recommended phase 3 treatment regimen [Срок оценки: Up to 3 years]

Вторичные конечные точки (7)

• Objective Response Rate (ORR) [Срок оценки: Up to 3 years]
• Duration of Response(DOR) [Срок оценки: up to 3 years]
• Disease Control Rate(DCR) [Срок оценки: up to 3 years]
• Progression-Free Survival(PFS) [Срок оценки: up to 3 years]
• 6-month Progression-Free Survival Rate [Срок оценки: up to 3 years]
• 6-month Overall Survival Rate [Срок оценки: up to 3 years]
• Assess the PK characteristics of Andamertinib [Срок оценки: On cycle1of day 1and cycle3of day1, samples were collected within 2 hours prior to dosing and 4 hours post-dosing,On Day 1of Cycle 2, Cycle 5, Cycle 7, and all subsequent odd-numbered cycles collected within 2hours prior to dosing(each cycle is 21days)]

Критерии участия

Критерии включения

• Age ≥18 years at the time of ICF signing.
• Histologically or cytologically confirmed, unresectable locally advanced (Stage IIIB or IIIC) or metastatic (Stage IV) non-squamous non-small cell lung cancer (NSCLC).
• Confirmed EGFR atypical mutation.
• No prior systemic therapy for locally advanced or metastatic NSCLC.
• At least one measurable lesion as defined by RECIST v1.1.
• ECOG PS ≤1.
• Life expectancy≥12 weeks.
• Adequate organ function confirmed within 7 days prior to the first dose of study treatment
• Female participants must use adequate contraceptive measures during study participation and for 90 days after the last dose of study treatment and must not be breastfeeding; female subjects not of childbearing potential must meet at least one of the following criteria at screening: Postmenopausal status; Documentation of irreversible surgical sterilization.
• Non-sterilized males: Abstinence or contraception use; No sperm donation.
• Willing and able to provide signed ICF and to comply with all requirements and restrictions listed in the ICF and this study protocol.

Критерии исключения

• Presence of specific genetic alterations for which approved targeted therapies are available.
• Recent participation (within 28 days) in another interventional clinical trial.
• Major surgery within 28 days prior to study entry or planned during the study period.
• Recent use of anti-tumor traditional proprietary medicine or local anti-tumor therapy.
• Need for specific concomitant medications (e.g., metformin) that cannot be paused during the study.
• History of another active malignancy within the past 5 years (except for specific cured cancers).
• Toxicities from prior therapy have not recovered to acceptable levels.
• Presence of symptomatic or uncontrolled brain metastases, carcinomatous meningitis, or spinal cord compression.
• Symptomatic and uncontrolled third-space fluid accumulations (e.g., pleural effusion, ascites).
• Severe cardiovascular/cerebrovascular disease or risk factors (e.g., heart failure, history of myocardial infarction, QT prolongation, uncontrolled hypertension, etc.).
• History or presence of interstitial lung disease, or drug/radiation-related pneumonitis.
• Active autoimmune or inflammatory diseases.
• Active, uncontrolled infection (including HBV, HCV, HIV, syphilis, tuberculosis, etc.).
• Gastrointestinal disorders or surgery affecting drug ingestion or absorption.
• Active keratitis or ulcerative keratitis.
• History of hypersensitivity to the study drug, its analogs, or chemotherapy drugs (pemetrexed/platinum agents).
• Recent administration (within 30 days) of a live attenuated vaccine.
• Psychiatric disorders or substance abuse potentially affecting compliance.
• Any other condition deemed by the investigator as unsuitable for study participation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Sun Yat-Sen University Cancer Center — Гуанчжоу

Идентификаторы

NCT: NCT07336732 · PLB1004-II/III-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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